This multidisciplinary program project will explore the biology of the lymphocyte on a broad front. We will focus primarily on the following areas. (1) Genetic control of lymphocyte surface antigens. (2) Immune responsiveness to these antigens. (3) Mechanisms of antigen recognition and cellular differentiation leading to immunity or tolerance. (4) Cellular interactions involved in cell mediated immunity. (5) The expression of tumor associated transplantation antigens and their relationship to the normal antigens on the cell surface. (6) Lymphocyte susceptibility to viral infection and the induction of murine leukemia. (7) Lymphoid cell differentiation in the ontogeny of immunity. (8) Ultrastructural studies with electromicroscopy of lymphocytes at various stages of differentiation. The overriding purpose of this program is to integrate these various approaches and relate them to clinical immunobiological problems.